Genome wide differences of gene expression associated with HLA-DRB1 genotype in multiple sclerosis: A pilot study

• Published in: Journal of neuroimmunology 2013-04, Vol.257 (1), p.90-96
• Main Authors: Apperson, Michelle L, Tian, Yingfang, Stamova, Boryana, Ander, Bradley P, Jickling, Glen C, Agius, Mark A, Sharp, Frank R
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Allergy and Immunology; Exon; Female; Gene Expression Regulation - immunology; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study - methods; Genotype; HLA-DRB1 Chains - biosynthesis; HLA-DRB1 Chains - genetics; HLA-DRB11501; Humans; Male; Microarray; Middle Aged; Multiple sclerosis; Multiple Sclerosis - diagnosis; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Neurology; Pilot Projects; RNA expression; Young Adult
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2013.02.004

Abstract Using two microarray platforms, we identify HLA-DRB5 as the most highly expressed gene in MS compared to healthy subjects. As expected, HLA-DRB5 expression was associated with the HLA-DRB1*1501 MS susceptibility allele. Besides HLA-DRB5, there were 1219 differentially expressed exons (p < 0.01, |fold change (FC)| > 1.2) that differed between HLA-DRB1*1501 Positive multiple sclerosis subjects (MSP) compared to HLA-DRB1*1501 negative multiple sclerosis subjects (MSN). Analysis of the regulated genes revealed significantly different immune signaling pathways including IL-4 and IL-17 in these two MS genotypes. Different risk alleles appear to be associated with different patterns of gene expression that may reflect differences in pathophysiology of these two MS subtypes. These preliminary data will need to be confirmed in future studies.